Characterization of a new antidementia β-secretase inhibitory peptide from Saccharomyces cerevisiae

In order to produce a potent antidementia β-secretase (BACE1) inhibitor from microorganisms, BACE1 inhibitory activities of cell-free extracts from many bacteria, yeasts and mushrooms were determined. Cell-free extracts of Saccharomyces cerevisiae K-7 exhibited the greatest BACE1 inhibitory activity of 64.2%. After purification of the BACE1 inhibitory peptides from S. cerevisiae K-7 using ultrafiltration, Sephadex G-10 column chromatography and reverse-phase HPLC, a purified BACE1 inhibitor with IC50 inhibitory activity of 72 ng (2.59 μM) was obtained with a 0.6% solid yield. The molecular mass of the purified BACE1 inhibitor was estimated to be 697 Da by LC–MS. It is a novel octapeptide with the sequence Gly-Pro-Leu-Gly-Pro-Ile-Gly-Ser, and does not show any similarity to the other BACE1 inhibitory peptide sequences. The purified BACE1 inhibitory peptide inhibited BACE1 non-competitively and was stable at 70 °C for 30 min, showing 75% of the residual BACE1 inhibitory activity.